PROJECT SUMMARY By some estimates, femoroacetabular impingement syndrome (FAIS) accounts for 82% of hip osteoarthritis (OA) cases. FAIS patients present with a loss of sphericity of the femoral head, reduction in femoral-neck offset, and/or an excessively prominent acetabular wall. Patients report pain that is position- or motion-related. Often, cartilage is delaminated from bone and the labrum is torn. The theory of FAIS pathophysiology is that pathoanatomy causes pathomechanics. However, we lack a quantitative understanding of the disease. Studies that have examined hip anatomy and biomechanics in FAIS patients have yielded conflicting data, likely due to the application of inaccurate measurement techniques. There is also a high prevalence of FAI morphology among the asymptomatic population (i.e., positive controls), which has hindered progress to understand why FAI morphology causes damage. Herein, we apply experimental and computational techniques to advance understanding of FAIS pathophysiology. We will examine three cohorts: FAIS patients, negative controls, and positive controls. Aim 1 will measure in-vivo hip articulation during inclined walking, pivoting, and squatting in the three cohorts using dual fluoroscopy. We hypothesize that patients with FAIS will exhibit altered kinematics; however, given our preliminary data, we posit that range of motion will not be reduced in patients. Further, we hypothesize that positive controls will have altered kinematics when compared to negative controls. In Sub-Aim 1, we will visualize the interaction between the shape of the hip joint and its kinematic position during dynamic loading using statistical shape modeling of the dual fluoroscopy data. Completion of Aim 1 improve clinical understanding of FAIS by enabling us to visualize the effects of pathologic shape during dynamic loading. Aim 2 will analyze chondrolabral mechanics in-silico to improve understanding of FAIS pathophysiology. Specifically, we will generate finite element models of bone, cartilage, and labrum using a validated pipeline. We will compare load transfer to the labrum and shear stresses and strains at the osteochondral and chondrolabral junction during inclined walking, pivoting, and squatting. We hypothesize that load transfer to the labrum is increased, and cartilage shear stresses and strains at the osteochondral and chondrolabral junctions are elevated in FAIS patients. Compensatory motion experienced by the positive control group may keep chondrolabral stresses and strains within normal. Thus, we hypothesize that there will be no significant differences in FE results between the two control groups. Sub-Aim 2 will quantify relationships between local measures of hip shape and chondrolabral mechanics. Completion of Aim 2 will enhance understanding of OA pathogenesis in patients with FAIS. Identifying how positive controls cope with their deformities could inform new treatment strategies.